Amplification of the gli gene in childhood sarcomas.
Amplification of the gli gene in childhood sarcomas.
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发表时间：
1989-10
期刊：
影响因子：
11.2
通讯作者：
Roberts Wm;E. Douglass;P. Sc;Peter J. Houghton;Look At
中科院分区：
文献类型：
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作者：
Roberts Wm;E. Douglass;P. Sc;Peter J. Houghton;Look At
gli基因最初通过其在人类恶性胶质瘤细胞中的扩增拷贝数来识别，其预测的翻译产物包含与Krüppel相关的五个串联DNA结合锌指基序，Krüppel是一个发育重要的果蝇分段基因。由于这种蛋白质的过度生产在肿瘤发展中的潜在重要性，我们检查了来自29例儿童肉瘤的DNA，以寻找gli基因扩增的证据。在研究的13个横纹肌肉瘤中，有一个含有gli基因的基因组DNA限制性片段扩增了约30倍，并鉴定了4.0-β-淀粉酶gli mRNA转录物的表达。gli基因扩增的肿瘤缺乏腺泡型或胚胎型横纹肌肉瘤的常见组织学特征;然而，培养中建立的肿瘤细胞的超微结构分析显示了减弱的肌节，类似于原始横纹肌母细胞中发现的肌节。该细胞系的细胞遗传学分析揭示了双微体染色质，在12号染色体长臂上的gli位点区域没有明显的重排，带q13至q14.3。一个15倍水平的gli扩增和gli mRNA转录也检测到一个建立的细胞系，从一个罕见的骨肉瘤患者的特点是多潜能的组织学特征。在来自该患者的冷冻保存的原代肿瘤细胞中观察到类似水平的gli基因扩增，证实基因扩增发生在肿瘤发育期间而不是在体外细胞培养期间。通过原位杂交将扩增的gli序列定位于衍生染色体7上的均匀染色区域。8例骨肉瘤和7例尤文氏肉瘤具有典型的组织病理学特征，没有一个有可检测到的gli序列重排或扩增。因此，儿童肉瘤中gli基因扩增似乎仅限于具有原始组织病理学特征的肿瘤，这可能反映了在早期间充质细胞发育过程中能够影响基因表达的基因产物的过度产生。
The gli gene, originally identified by its amplified copy number in cells from a human malignant glioma, has a predicted translation product that contains five tandem DNA-binding zinc finger motifs related to those of Krüppel, a developmentally important Drosophila segmentation gene. Because of the potential importance of overproduction of this protein in neoplastic development, we examined DNAs from 29 cases of childhood sarcoma for evidence of amplification of the gli gene. In one of the 13 rhabdomyosarcomas studied, genomic DNA restriction fragments containing the gli gene were amplified approximately 30-fold, and expression of the 4.0-kilobase gli mRNA transcript was identified. The tumor with gli gene amplification lacked the usual histological features of alveolar or embryonal rhabdomyosarcoma; however, ultrastructural analysis of tumor cells established in culture revealed attenuated sarcomeres, resembling those found in primitive rhabdomyoblasts. Cytogenetic analysis of this cell line disclosed double-minute chromatin bodies, with no apparent rearrangements in the region of the gli locus on the long arm of chromosome 12, bands q13 to q14.3. A 15-fold level of gli amplification and gli mRNA transcripts were also detected in an established cell line from a patient with a rare form of osteosarcoma characterized by multipotential histological features. A similar level of gli gene amplification was observed in cryopreserved primary tumor cells from this patient, confirming that gene amplification took place during tumor development and not during in vitro cell culture. Amplified gli sequences were cytogenetically localized by in situ hybridization to a homogeneously staining region contained on a derivative chromosome 7. Of eight osteosarcomas and seven Ewing's sarcomas with typical histopathological features, none had detectable rearrangements or amplification of gli sequences. Thus, gli gene amplification in childhood sarcomas appears restricted to tumors with primitive histopathological features, perhaps reflecting overproduction of a gene product able to influence gene expression during early mesenchymal cell development.